Total neoadjuvant immunotherapy plus chemotherapy in Borrmann type IV gastric cancer (PERISCOPE-01 study): An open-label, single-arm, phase 2 trial.

4079 Background: Borrmann type IV (Borrmann-IV) gastric cancer (GC), or linitis plastica, is marked by diffuse infiltration, early metastasis, and poor prognosis, with limited benefit from conventional therapies. This study evaluated the efficacy and safety of a total neoadjuvant regimen combining immunotherapy and chemotherapy in Borrmann-IV GC. Methods: This trial (NCT06451211) enrolled patients with Borrmagnn-IV gastric cancer without distant metastasis. Participants received a total neoadjuvant regimen consisting of tislelizumab (an anti–PD-1 antibody) combined with platinum-based chemotherapy (oxaliplatin plus capecitabine or S-1) for 6 cycles at 3-week intervals, followed by radical surgical resection. The prespecified primary endpoint was the pathological response rate, defined as tumor regression grade (TRG) 0/1. Results: A total of 56 patients were enrolled, all patients had no distant metastasis confirmed by laparoscopic exploration and ascitic fluid cytology. The median age was 58 years; all patients were pMMR. In the efficacy analysis population (n=47), 41 patients completed 5–6 cycles and 6 patients completed 3–4 cycles of preoperative chemotherapy plus immunotherapy, no patients experienced disease progression leading to tumor metastasis during preoperative treatment. 47 patients underwent radical surgical resection, including 42 total gastrectomy, with an R0 resection rate of 98% (46/47). The prespecified primary endpoint of TRG 0/1 was achieved in 32% of patients (15/47; 95% CI, 21%–48%). Notably, 17% (n = 8) achieved pCR (ypT0N0), and 53% (n =25) were ypN0. Pathological response (TRG 0/1) was significantly higher in Lauren intestinal/mixed versus diffuse types (53% vs. 21%; p < 0.05), while efficacy was comparable between PD-L1 CPS ≥5 and <5 (44% vs. 30%). Grade 3/4 treatment-related adverse events occurred in 32% of patients (n=18), mainly thrombocytopenia and liver function impairment. Surgical morbidity (Clavien–Dindo grade II/III) occurred in 10.6% of surgical patients (5/47), including 1 patient with postoperative bleeding and 3 patients with anastomotic leakage; no perioperative mortality was observed. Conclusions: Total neoadjuvant tislelizumab plus chemotherapy demonstrated promising efficacy and an acceptable safety profile in patients with Borrmann-IV gastric cancer. Lauren classification may serve as a potential predictive biomarker and warrants further study. Clinical trial information: NCT06451211 .